DESCRIPTION: Neural cells exhibit highly polarized morphology and functions which undergo plastic changes in response to external stimuli. This is the basis for neurogenesis, gliogenesis, synaptogenesis, myelin morphogenesis, gliosis, synaptic plasticity and learning and memory. Intracellular trafficking and localized translation of specific mRNAs play a key role in establishing and maintaining morphological and functional polarity and in mediating plasticity. This is a proposal to investigate the molecular mechanisms of intracellular trafficking and localized translation of myelin basic protein (MBP) mRNA in oligodendrocytes. MBP mRNA follows a defined multistep intracellular trafficking pathway from the nucleus through the perikaryon and processes to the myelin compartment. One particular cis-acting sequence in the 3'UTR of MBP mRNA, termed the RNA transport/transplantation sequence (RTS), is involved in several steps of this pathway. Several other transported RNAs also contain RTS-like sequences. The RTS binds to the trans-acting factor, hnRNPA2 (A2). The overall goal of the proposal is to elucidate how TRS/A2 determinants are involved in intracellular RNA trafficking in oligodendrocytes. The results will provide a paradigm for understanding intracellular RNA trafficking in neural cells in general. This will be important for elucidating the molecular mechanisms mediating polarity and plasticity in the nervous system.